The VI AMMCS International Conference
Waterloo, Ontario, Canada | August 14-18, 2023
AMMCS 2023 Plenary Talk
Combined multiscale modeling and experimental study of regulation mechanisms of shape and structure formation during tissue development
Mark Alber (University of California Riverside)
The regulation and maintenance of an organ's shape and structure is a major outstanding question in developmental biology. The Drosophila wing imaginal disc serves as a powerful system for elucidating design principles of the shape formation in epithelial morphogenesis. Yet, even simple epithelial systems such as the wing disc are extremely complex. A tissue's shape and structure emerge from the integration of many biochemical and biophysical interactions between proteins, subcellular components, and cell-cell and cell-ECM interactions. How cellular mechanical properties affect tissue size and patterning of cell identities on the apical surface of the wing disc pouch has been intensively investigated. However, less effort has focused on studying the mechanisms governing the shape of the wing disc in the cross-section. Both the significance and difficulty of such studies are due in part to the need to consider the composite nature of the material consisting of multiple cell layers and cell-ECM interactions as well as the elongated shape of columnar cells. Results obtained using iterative approach combining multiscale computational modelling and quantitative experimental approach will be used in this talk to discuss direct and indirect roles of subcellular mechanical forces, nuclear positioning, and extracellular matrix in shaping the major axis of the wing pouch during the larval stage in fruit flies, which serves as a prototypical system for investigating epithelial morphogenesis. The research findings demonstrate that subcellular mechanical forces can effectively generate the curved tissue profile, while extracellular matrix is necessary for preserving the bent shape even in the absence of subcellular mechanical forces once the shape is generated. The developed integrated multiscale modelling environment can be readily extended to generate and test hypothesized novel mechanisms of developmental dynamics of other systems, including organoids that consist of several cellular and extracellular matrix layers.
Professor Mark Alber earned his Ph.D. in mathematics at the University of Pennsylvania under the direction of J. E. Marsden (UC Berkeley and Caltech). He held several positions at the University of Notre Dame including most recently Vincent J. Duncan Family Chair in Applied Mathematics. He is currently Distinguished Professor in the Department of Mathematics and Director of the Center for Quantitative Modeling in Biology, University of California, Riverside. Dr. Alber was elected in 2011 Fellow of the American Association for the Advancement of Science (AAAS) and was recently selected for the 2023-24 Fulbright Scholar Award. He is currently a section editor in systems biology of PLoS Computational Biology and member of editorial boards of Bulletin of Mathematical Biology and Biophysical Journal. His research interests include mathematical and computational multiscale modeling of plants and epithelial tissue development as well as blood clot formation and contraction.